Biofeedback therapy is an instrument-based learning process centered on operant conditioning. The goal of biofeedback therapy in defecatory disorders is to strengthen the pelvic floor muscles, retrain rectal sensation and coordinate pelvic floor muscles during evacuation. Biofeedback therapy, in a broader sense, includes education, counseling, and diaphragmatic muscle training as well as exercise, sensory, and coordination training. For dyssynergic defecation, biofeedback therapy is a well-known and useful treatment option that had response rates of approximately 70-80% in randomized controlled trials. Biofeedback therapy for dyssynergic defecation consists of improving the abdominal push effort together with biofeedback technique-guided pelvic floor relaxation followed by simulated defecation and/or sensory training. For fecal incontinence, the results of a randomized controlled trial, which had a response rate of 76%, indicated that biofeedback therapy is useful in selected patients who fail to respond to conservative treatment and that training to enhance rectal discrimination of sensation may be helpful in reducing fecal incontinence. The focus of biofeedback therapy for fecal incontinence is on exercising external sphincter contractions under instant feedback, either alone or synchronously with rectal distension and/or sensory training. Biofeedback therapy is a safe treatment that may produce durable improvement beyond the active treatment period; however, a well-designed study to establish a standard protocol for biofeedback therapy is needed. This review discusses the technique of biofeedback therapy to achieve the goal and clinical outcomes for constipation and fecal incontinence.
Biofeedback, Psychology* ; Conditioning, Operant ; Constipation* ; Counseling ; Defecation ; Discrimination (Psychology) ; Fecal Incontinence* ; Humans ; Learning ; Muscles ; Pelvic Floor ; Relaxation ; Sensation ; Treatment Outcome

Animals ; Conditioning, Classical ; Evoked Potentials, Somatosensory ; Fear ; psychology ; Male ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological

OBJECTIVETo investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference.

METHODSMorphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods.

RESULTSEight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas.

CONCLUSIONIt was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve activation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.

Analgesics, Opioid ; pharmacology ; Animals ; Blotting, Western ; Conditioning (Psychology) ; Conditioning, Operant ; drug effects ; Cyclic AMP Response Element-Binding Protein ; biosynthesis ; Hippocampus ; metabolism ; Male ; Morphine ; pharmacology ; Nucleus Accumbens ; metabolism ; Prefrontal Cortex ; metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors

OBJECTIVETo explore neurobiological mechanisms of the withdrawal-induced aversion. The changes of protein kinase A were measured in central amygdaloid nucleic (CeA) of conditioned place aversion (CPA) model rats.

METHODS(1) All 72 male SD rats were divided into three groups, model group (MN group), and control group (MS group and SN group). MN group was injected with morphine,6.5 days, 10 mg/kg, intraperitoneally (ip), twice per day, naloxone injection, 0.3 mg/kg, ip, along with conditioned place aversion training, to develop the CPA model. The MS group was administrated equivalent volume of morphine and saline. Also the SN group was injected with equivalent volume of saline and naloxone. (2) During the process of morphine-induced CPA, the expression of protein kinase A was assayed with immunohistochemistry in the CeA.

RESULTSIn the MN group, protein kinase A expressions in the CeA occurred adaptive changes at different points of CPA (P < 0.05). Protein kinase A expressions after establishment(Day7,134.43 +/- 4.481, P < 0.05), and after extinction (Day 13, 141.01 +/- 3.360, P < 0.01), and after reinstatement (Day 14,137.18 +/- 40.330, P < 0.05) were also lower than those before the establishment of the CPA (Day 5, 124.48 +/- 6.722). However, PKA expressions were not significantly different both in MS group (P > 0.05)and SN group (P > 0.05).

CONCLUSION(1) Protein kinase A expression, in turn regulating the aversion expression, in the CeA probably is a key pathway contributing to the development of CPA. (2) The neuroadaptation mediated by protein kinase A may be one of the important molecular underpinnings of CPA.

Amygdala ; enzymology ; Animals ; Conditioning, Operant ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Disease Models, Animal ; Extinction, Psychological ; Male ; Morphine Dependence ; psychology ; Rats ; Rats, Sprague-Dawley

Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine.
Animals ; Cocaine ; Conditioning, Classical ; Conditioning, Operant ; Memory ; Motivation ; Rats ; Reward ; Self Administration ; Sucrose

OBJECTIVETo study the acting mechanism of anti-morphine conditioned place preference (CPP) between aqueous extract of Corydalis yanhusuo and L-THP and compare their effects.

METHODThe CPP model was established by injecting morphine in rats with a increasing dose for 10 days, with the initial dose of 10 g x kg(-1) and the final dose of 100 g x kg(-1), 10 mg x kg(-1) was increased each day, thus 100 mg x kg(-1) was injected by d 10. Having been treated with differential doses (2, 1 and 0.5 g x kg(-1)) of C. yanhusuo (containing L-THP: 0.153, 0.077 and 0.038 mg x kg(-1) respectively) and L-THP (3.76, 1.88 and 0.94 mg x kg(-1)) for six days, the CPP effect in rats was detected. Both colorimetry and immunohistochemistry methods were adopted to detect the content of glutamate neurotransmitter in each brain region and the expression of NR2B in VTA-NAc-PFC neuroanatomical circuit.

RESULTCompared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76 and 1.88 mg x kg(-1)) groups showed a notably shorter retention period of rats in white boxes (morphine-accompanied boxes) (P < 0.05 or P < 0.01) and remarkably lower glutamic acid content in VTA, NAc and PFC and NR2B expression.

CONCLUSIONBoth C. yanhusuo and L-THP can substantially inhibit the effect of morphine CPP, reduce the increasing glutamic acid content in VTA-NAc-PFC neuroanatomical circuit and down-regulated NR2B expression, which may be one of mechanisms on reducing the effect of morphine CPP. C. yanhusuo preparations containing L-THP (1 x ) showed 24-fold effect of L-THP monomer of single application in terms of the behaviouristics of inhibitory effect on CPP as well as the similarity in terms of transmitter glutamic acid of in VTA-NAc-PFC neuroanatomical circuit and pharmacological mechanism of NR2B.

Animals ; Berberine Alkaloids ; therapeutic use ; Conditioning, Operant ; drug effects ; Corydalis ; chemistry ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Morphine ; antagonists & inhibitors ; Morphine Dependence ; drug therapy ; psychology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects.

METHODThe CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors.

RESULTCompared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P < 0.01 or P < 0.05), and revealed a remarkably lower dopamine content in VTA, NAc and PFC and the significant increase in the expression of D2 receptor (P < 0.01 or P < 0.05).

CONCLUSIONThe down-regulation of the increased dopamine content in reward nervous circuitry and the up-regulation of the expression of D2 receptor may be one of mechanisms of C. yanhusuo and L-THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.

Animals ; Berberine Alkaloids ; administration & dosage ; Brain ; drug effects ; metabolism ; physiopathology ; Conditioning, Operant ; drug effects ; Corydalis ; chemistry ; Dopamine ; metabolism ; Humans ; Male ; Morphine ; adverse effects ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2 ; genetics ; metabolism ; Substance-Related Disorders ; drug therapy ; genetics ; metabolism ; psychology

Allogeneic bone marrow or peripheral blood stem cell transplantation traditionally uses myeloablative regimen for conditioning to enable grafting of donor's stem cells. Animal experiments have shown that a milder non-myeloablative conditioning regimen does allow engraftment to occur. Nonmyeloablative conditioning regimens are low-intensity immunosuppressive treatment given to the recipient before infusion of donor's stem cells. It was reported to have decreased immediate procedural mortality, in particular those secondary to acute graft versus host reaction. However, it did give rise to higher risks of graft rejection, tumour tolerance and disease progression. Fortunately, appropriately administered donor lymphocyte infusion has been shown to establish full donor chimerism (complete donor stem cell grafting in the recipient's bone marrow) and potentiate antitumour effect (graft versus tumour reaction). The reduction of immediate transplant mortality allows the procedure to be carried out in older age groups, patients with concomitant diseases that otherwise would have made the patients unfit for the procedure, patients with non-malignant disorders such as congenital immune deficiencies, autoimmune disorders or thalassaemia majors. The regimen also allows transplantation of genetically manipulated haemopoietic stem cells (gene thrapy) to be carried out more readily in the immediate future. Lastly, the regimen may serve as a platform for immunotherapy using specific T cell clones for anti-tumour therapy with or without the knowledge of known tumour antigen.
seconds ; regimen ; Conditioning (Psychology) ; Stem Cells ; Exertional dyspnea

Amygdala ; drug effects ; metabolism ; Animals ; Conditioning (Psychology) ; Morphine ; adverse effects ; Rats ; Receptors, Opioid, kappa ; metabolism

OBJECTIVETo study the correlation between EEG characteristics of medial prefrontal cortex (mPFC) and drug-seeking behavior of rats with morphine dependent place preference under shuttling condition.

METHODSForty rats were randomly divided into four groups (n = 10): morphine PL group, NS PL group, morphine IL group and NS IL group. After embeding the electrode in prelimbic (PL) or infralimbic (IL) cortex of each group by brain stereotaxic operation, the model of morphine dependent conditioned place preference (CPP) in rats was established. The differences of EEG wave percentage in mPFC were telemetered and analyzed when rats shuttled before and after the model.

RESULTSAfter the model, the withdrawal symptoms were evident in morphine PL and IL group, and the activity time and distance in white box were increased obviously. Compared with control group, after the model, the EEG in morphine PL group showed that: when the rats shuttled to white box, 8 wave decreased obviously, P wave increased obviously. When the rats shuttled to black box, brain waves showed opposite changes. The EEG in morphine IL group showed that: when the rats shuttled to white box, a wave increased obviously, P and a wave decreased obviously. When the rats shuttled to black box, the brain wave had no significant differences compared with control group.

CONCLUSIONThe EEG changes are different in PL and IL cortex of morphine CPP rats under shuttling condition, and the EEG changes are also different when rats shuttling to white or black box. There is possibly different mechanism, when different drug-seeking environmental cues caused EEG changes in different regions of mPFC.

Animals ; Conditioning (Psychology) ; Cues ; Drug-Seeking Behavior ; Electroencephalography ; Morphine Dependence ; physiopathology ; Prefrontal Cortex ; physiopathology ; Rats ; Telemetry